Entinostat, Lapatinib Ditosylate and Trastuzumab in Treating Patients With Locally Recurrent or Distant Relapsed Metastatic Breast Cancer Previously Treated With Trastuzumab Only
17. Mai 2019 aktualisiert von: National Cancer Institute (NCI)
Phase I and Phase I Trastuzumab Cohort Study of Entinostat, Lapatinib and Trastuzumab in Patients With HER2-Positive Metastatic Breast Cancer in Whom Trastuzumab Has Failed
This phase I trial studies the side effects and best dose of entinostat when given together with lapatinib ditosylate and trastuzumab in treating patients with breast cancer that has spread from the original (primary) tumor to distant organs or distant lymph nodes or has recurred (come back) at or near the same place as the original (primary) tumor, usually after a period of time during which the cancer could not be detected.
Entinostat and lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Monoclonal antibodies, such as trastuzumab, may interfere with the ability of tumor cells to grow and spread.
Giving entinostat together with lapatinib ditosylate and trastuzumab may kill more tumor cells.
Studienübersicht
Status
Abgeschlossen
Bedingungen
Intervention / Behandlung
Detaillierte Beschreibung
PRIMARY OBJECTIVES:
I. To determine the recommended phase II dose (RP2D) for entinostat in combination with lapatinib (lapatinib ditosylate) in patients whom trastuzumab has failed for human epidermal growth factor receptor 2+ (HER2+) metastatic breast cancer (Phase I).
II. To determine the maximum tolerated dose (MTD) for entinostat in combination with lapatinib and trastuzumab in patients whom trastuzumab has failed for HER2+ metastatic breast cancer (Phase I Trastuzumab Cohort).
SECONDARY OBJECTIVES:
I. To determine the toxicity of combination therapy with entinostat and lapatinib in patients whom trastuzumab has failed for HER2+ metastatic breast cancer (Phase I).
II. To determine the toxicity of entinostat in combination with lapatinib and trastuzumab in patients whom trastuzumab has failed for HER2+ metastatic breast cancer (Phase I Trastuzumab Cohort).
EXPLORATORY OBJECTIVES:
I. Determine whether the 2-drug combination modulates the expression of HER2, phosphorylated HER2 (pHER), epidermal growth factor receptor (EGFR), phosphorylated EGFR (pEGFR), v-akt murine thymoma viral oncogene homolog 1 (Akt), and phosphorylated Akt (pAkt) in breast tumors and/or circulating tumor cells (CTCs).
OUTLINE: This is a dose-escalation study of entinostat.
Patients receive entinostat orally (PO) on days 1 and 15 and lapatinib tosylate PO on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients in the Phase I trastuzumab cohort also receive maintenance dose of trastuzumab intravenously (IV) over 30-90 minutes every 3 weeks.
After completion of study treatment, patients are followed up for 28 days or until toxicities are resolved.
Studientyp
Interventionell
Einschreibung (Tatsächlich)
37
Phase
- Phase 1
Kontakte und Standorte
Dieser Abschnitt enthält die Kontaktdaten derjenigen, die die Studie durchführen, und Informationen darüber, wo diese Studie durchgeführt wird.
Studienorte
-
-
Texas
-
Houston, Texas, Vereinigte Staaten, 77030
- M D Anderson Cancer Center
-
-
Teilnahmekriterien
Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.
Zulassungskriterien
Studienberechtigtes Alter
18 Jahre und älter (Erwachsene, Älterer Erwachsener)
Akzeptiert gesunde Freiwillige
Nein
Studienberechtigte Geschlechter
Alle
Beschreibung
Inclusion Criteria:
- Patients have histological confirmation of invasive breast carcinoma
- Patients have locally recurrent or distant relapsed metastatic disease
- Patients have positive HER2 expression by immunohistochemistry (IHC) (3+) or fluorescence in situ hybridization (FISH) testing (> 2.0 ratio)
- Patients are able to swallow and retain oral medication (i.e., no uncontrolled vomiting, inability to swallow, or diagnosis of chronic malabsorption)
- Patients have Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Patients must have received prior trastuzumab for > 2 month period before disease recurrence or recurrence or progression while on trastuzumab-based therapy
- Patients have ability and willingness to sign written informed consent
- Female patients of childbearing potential (a female not free from menses > 2 years or not surgically sterilized) must be willing to use an adequate barrier method of contraception to prevent pregnancy or agree to abstain from heterosexual activity throughout the study; male patients who are able to father children must use an adequate barrier method of contraception
- Female patients of childbearing potential must have negative serum pregnancy test within 14 days of starting protocol therapy
- Patients with brain metastasis have no signs of progressive disease 4 months after the completion of brain metastasis treatment (radiation therapy, surgery, etc.) do not require anticonvulsants or corticosteroids, and have been off such drugs for at least 7 days
- Both men and women and members of all races and ethnic groups are eligible for this trial
Exclusion Criteria:
- Patients are receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy, biological therapy and hormonal therapy) while taking study medication
- Serum bilirubin >= 1.5 x upper limit of normal (ULN)
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >= 3 x ULN (with or without liver metastasis [mets])
- Absolute neutrophil count (ANC) < 1.5
- Hemoglobin =< 9
- Platelet =< 140,000
- Patients have an active infection and require intravenous (IV) or oral antibiotics
- Cardiac arrhythmia requiring maintenance medication
- History of gastrointestinal disorders (medical disorders or extensive surgery) which may interfere with the absorption of the study drug
- Patients have a concurrent disease or condition that would make them inappropriate for study participation, or any serious medical disorder that would interfere with patients' safety
- Serum creatinine > 2.0 mg/dL
Studienplan
Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: N / A
- Interventionsmodell: Einzelgruppenzuweisung
- Maskierung: Keine (Offenes Etikett)
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
|---|---|
|
Experimental: Treatment (entinostat, lapatinib ditosylate and trastuzumab)
Patients receive entinostat PO on days 1 and 15 and lapatinib tosylate PO on days 1-28.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients in the Phase I Trastuzumab Cohort also receive maintenance dose of trastuzumab IV over 30-90 minutes every 3 weeks.
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Korrelative Studien
Gegeben IV
Andere Namen:
PO gegeben
Andere Namen:
PO gegeben
Andere Namen:
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Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
|---|---|
|
RP2D for entinostat in combination with lapatinib ditosylate defined as the highest dose level in which 6 patients have been treated with at most 1 patient experiencing dose limiting toxicity
Zeitfenster: Up to 28 days
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Up to 28 days
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
|---|---|
|
Incidence of grade III or IV toxicities, graded according to Common Terminology Criteria for Adverse Events version 4
Zeitfenster: Up to 28 days
|
Up to 28 days
|
Andere Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Changes in CTCs levels before and after the combination treatment of entinostat, lapatinib ditosylate and trastuzumab
Zeitfenster: Baseline up to 28 days after completion of study treatment
|
Summary statistics (mean, standard deviation, median, quartiles) will be summarized for these changes in CTCs and biomarkers by patient tumor response status (yes vs. no).
Changes will be compared between the two groups of patients (yes vs. no tumor response) using the two-sample t-test.
If the data is skewed, Wilcoxon rank-sum test will be used.
|
Baseline up to 28 days after completion of study treatment
|
|
Changes in phosphorylated Akt levels before and after the combination treatment of entinostat, lapatinib ditosylate and trastuzumab.
Zeitfenster: Baseline up to 28 days after completion of study treatment
|
Summary statistics (mean, standard deviation, median, quartiles) will be summarized for these changes in CTCs and biomarkers by patient tumor response status (yes vs. no).
Changes will be compared between the two groups of patients (yes vs. no tumor response) using the two-sample t-test.
If the data is skewed, Wilcoxon rank-sum test will be used.
|
Baseline up to 28 days after completion of study treatment
|
|
Changes in phosphorylated HER2 levels before and after the combination treatment of entinostat, lapatinib ditosylate and trastuzumab
Zeitfenster: Baseline up to 28 days after completion of study treatment
|
Summary statistics (mean, standard deviation, median, quartiles) will be summarized for these changes biomarkers by patient tumor response status (yes vs. no).
Changes will be compared between the two groups of patients (yes vs. no tumor response) using the two-sample t-test.
If the data is skewed, Wilcoxon rank-sum test will be used.
|
Baseline up to 28 days after completion of study treatment
|
|
Changes in phosphorylated EGFR levels before and after the combination treatment of entinostat, lapatinib ditosylate and trastuzumab
Zeitfenster: Baseline up to 28 days after completion of study treatment
|
Summary statistics (mean, standard deviation, median, quartiles) will be summarized for these changes biomarkers by patient tumor response status (yes vs. no).
Changes will be compared between the two groups of patients (yes vs. no tumor response) using the two-sample t-test.
If the data is skewed, Wilcoxon rank-sum test will be used.
|
Baseline up to 28 days after completion of study treatment
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Mitarbeiter und Ermittler
Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.
Sponsor
Studienaufzeichnungsdaten
Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.
Haupttermine studieren
Studienbeginn (Tatsächlich)
10. Januar 2012
Primärer Abschluss (Tatsächlich)
16. Februar 2016
Studienabschluss (Tatsächlich)
16. Februar 2016
Studienanmeldedaten
Zuerst eingereicht
13. September 2011
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
13. September 2011
Zuerst gepostet (Schätzen)
14. September 2011
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
20. Mai 2019
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
17. Mai 2019
Zuletzt verifiziert
1. Mai 2019
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
- Hautkrankheiten
- Neubildungen nach histologischem Typ
- Neubildungen
- Neubildungen nach Standort
- Neubildungen, Drüsen und Epithelien
- Brusterkrankungen
- Neoplasien der Brust
- Karzinom
- Physiologische Wirkungen von Arzneimitteln
- Molekulare Mechanismen der pharmakologischen Wirkung
- Enzym-Inhibitoren
- Antineoplastische Mittel
- Immunologische Faktoren
- Proteinkinase-Inhibitoren
- Trastuzumab
- Antikörper
- Immunglobuline
- Antikörper, monoklonal
- Antineoplastische Mittel, immunologische
- Trastuzumab-Biosimilar HLX02
- Histon-Deacetylase-Inhibitoren
- Entinostat
- Lapatinib
Andere Studien-ID-Nummern
- NCI-2011-03222 (Registrierungskennung: CTRP (Clinical Trial Reporting Program))
- P30CA016672 (US NIH Stipendium/Vertrag)
- UM1CA186688 (US NIH Stipendium/Vertrag)
- U01CA062461 (US NIH Stipendium/Vertrag)
- 8871 (Andere Kennung: CTEP)
- NCI 8871
- 2010-0842 (Andere Kennung: M D Anderson Cancer Center)
- CDR0000710891
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